Ellagic acid

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Ellagic acid

For Patients & Caregivers

How It Works

Ellagic acid is found in many foods that are part of a healthy diet, but there is no evidence to support its use for cancer treatment.

Ellagic acid is a naturally occurring compound called a tannin, found in red raspberries, strawberries, pomegranates, and walnuts. In laboratory studies, ellagic acid showed  antiviral, antibacterial and antioxidant and cancer-preventive properties.

Small clinical studies have shown that ellagic acid may lower cholesterol and decrease lipid peroxidation in patients with metabolic syndrome; and may help restore cognitive performance associated with mild age-related decline. Consuming red raspberries may help improve endothelial function.
 

Purported Uses
  • To prevent cancer
    Although laboratory and animal studies suggest that ellagic acid has anti-cancer properties, human data are lacking.
  • To lower cholesterol
    One study found that consumption of a drink made with freeze-dried strawberry powder for 4 weeks lowered total cholesterol and LDL levels in obese women with metabolic syndrome. Further research is needed to confirm this effect.
Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450: Ellagic acid inhibits cytochrome P450  2A2, 3A1, 2C11, 2B1, 2B2 and 2C6 enzymes, and may increase the risk of side effects of these drugs. Clinical relevance is not known.
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For Healthcare Professionals

Clinical Summary

A phenolic compound derived from ellagitannins commonly found in red raspberries, strawberries, pomegranates, and walnuts, ellagic acid has antiviral, antibacterial and antioxidant properties (1) (2) (8). Small clinical studies have shown that it may lower cholesterol and decrease lipid peroxidation in patients with metabolic syndrome (7); and may help restore cognitive performance associated with mild age-related decline (18). In addition, consumption of red raspberries was associated with improvements in endothelial function (19); and a pomegranate extract may have beneficial effects by inducing ellagitanin metabolite formation and changing microbiota (20).

Pre-clinical studies indicate anticarcinogenic effects of ellagic acid against liver, esophageal, prostate, and colorectal cancer cell lines (3) (4) (5) (6). It was also shown to induce apoptosis and potentiate all-trans retinoic acid myeloid differentiation therapy in human leukemia HL-60 cells (9). In another study, pomegranate-derived ellagitannins exhibited anti-aromatase activity and suppressed testosterone-induced breast cancer cell proliferation, but ellagic acid did not have such effects  (10).
In an exploratory study of patients with biochemically recurrent prostate cancer, grape skin comprising ellagic acid, quercetin, and resveratrol was reported to be safe and to affect a non-significant increase in prostate-specific antigen doubling time (21). Further research is needed to assess the anticancer potential of ellagic acid.

Food Sources

Red raspberries, strawberries, pomegranates, walnuts

Purported Uses
  • Cancer prevention
  • Hypercholesterolemia
Mechanism of Action

Ellagic acid appears to inhibit chemical-induced esophageal carcinogenesis in animals (11). It down-regulates insulin-like growth factor IGF-II (6) and activates p53/p21 expression, leading to cell cycle arrest at the G1/S phase and apoptosis (12). In vitro studies report that ellagic acid protects cells from oxidative DNA damage caused by hydrogen peroxide and bleomycin (8). Ellagic acid’s ability to induce detoxification enzymes NADPH and quinone reductase contribute to some of its chemopreventive activities (13). Conversely, certain cytochrome P450 enzymes are inhibited by ellagic acid, preventing other carcinogens from being metabolized into more mutagenic forms (14) (15).

Herb-Drug Interactions
  • Cytochrome P450 substrates: Ellagic acid inhibits cytochrome P450  2A2, 3A1, 2C11, 2B1, 2B2 and 2C6, and can affect the intracellular concentration of drugs metabolized by these enzymes (14) (15). Clinical relevance is not known.
Dosage (OneMSK Only)
References
  1. Atta UR, et al. New antioxidant and antimicrobial ellagic acid derivatives from Pteleopsis hylodendron. Planta Medica 2001;67:335-9.
  2. Akiyama H, et al. Antibacterial action of several tannins against Staphylococcus aureus. J Antimicrob Chemother 2001;48:487-91.
  3. Tanaka T, et al. Inhibitory effect of ellagic acid on N-2-fluorenylacetamide-induced liver carcinogenesis in male ACI/N rats. Jpn J Cancer Res 1988;79:1297-303.
  4. Stoner GD, et al. Isothiocyanates and freeze-dried strawberries as inhibitors of esophageal cancer. Toxicol Sci 1999;52(2 Suppl):95-100.
  5. Narayanan BA, et al. Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci 2002;70:1821-39.
  6. Narayanan BA, Re GG. IGF-II down regulation associated cell cycle arrest in colon cancer cells exposed to phenolic antioxidant ellagic acid. Anticancer Res 2001;21:359-64.
  7. Basu A, Wilkinson M, Penugonda K, et al. Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic sndrome: baseline and post intervention effects. Nutr Journal. 2009 Sept;8:43.
  8. Festa F, et al. Strong antioxidant activity of ellagic acid in mammalian cells in vitro revealed by the comet assay. Anticancer Res 2001;21:3903-8.
  9. Hagiwara Y, Kasukabe T, Kaneko Y, Niitsu N, Okabe-Kado J. Ellagic acid, a natural polyphenolic compound, induces apoptosis and potentiates retinoic acid-induced differentiation of human leukemia HL-60 cells. Int J Hematol. 2010 Jul;92(1):136-43.
  10. Adams LS, Zhang Y, Seeram NP, Heber D, Chen S. Pomegranate ellagitannin-derived compounds exhibit anti proliferative and anti-aromatase activity in breast cancer cells in vitro. Cancer Prev Res. 2010 Jan;3(1):108-113.
  11. Siglin JC, et al. Effects of dietary phenethyl isothiocyanate, ellagic acid, sulindac and calcium on the induction and progression of N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats. Carcinogenesis 1995;16:1101-6.
  12. Narayanan BA, et al. p53/p21(WAF1/CIP1) expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells. Cancer Lett 1999;136:215-21.
  13. Barch DH, Rundhaugen LM. Ellagic acid induces NAD(P)H:quinone reductase through activation of the antioxidant responsive element of the rat NAD(P)H:quinone reductase gene. Carcinogenesis 1994;15:2065-8.
  14. Zhang Z, et al. Inhibition of liver microsomal cytochrome P450 activity and metabolism of the tobacco-specific nitrosamine NNK by capsaicin and ellagic acid. Anticancer Res 1993;13:2341-6.
  15. Barch DH, et al. Dietary ellagic acid inhibits the enzymatic activity of CYP1A1 without altering hepatic concentrations of CYP1A1 or CYP1A1 mRNA. Biochem Biophys Res Commun 1994;201:1477-82.
  16. Boukharta M, Jalbert G, Castonguay A. Biodistribution of ellagic acid and dose-related inhibition of lung tumorigenesis in A/J mice. Nutr Cancer 1992;18:181-9.
  17. Doyle B, Griffiths LA. The metabolism of ellagic acid in the rat. Xenobiotica 1980;10:247-56.
  18. Liu Y, Yu S, Wang F, et al. Chronic administration of ellagic acid improved the cognition in middle-aged overweight men. Appl Physiol Nutr Metab. 2018 Mar;43(3):266-273.
  19. Istas G, Feliciano RP, Weber T, et al. Plasma urolithin metabolites correlate with improvements in endothelial function after red raspberry consumption: A double-blind randomized controlled trial. Arch Biochem Biophys. 2018 Aug 1;651:43-51.
  20. Li Z, Henning SM, Lee RP, et al. Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers. Food Funct. 2015 Aug;6(8):2487-95.
  21. Paller CJ, Rudek MA, Zhou XC, et al. A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination. Prostate. 2015 Oct;75(14):1518-25.
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